Evidence map›Paper›PMID 25072259›Full record

ArticleBritish journal of cancer2014

Glutamine depletion by crisantaspase hinders the growth of human hepatocellular carcinoma xenografts.

M Chiu, S Tardito, S Pillozzi, A Arcangeli, A Armento, J Uggeri, G Missale, M G Bianchi, A Barilli, V Dall'Asta and 5 more

Open access · hybridAbstract read
In one paragraph

Article in British journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
1.8field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

48 citing papers in PubMed, 84 citations in OpenAlex.

  1. Review
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  5. Deep Learning-aidedMagnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine · 2025
    Article
  6. Review
  7. Article
  8. Hepatocellular carcinoma: signaling pathways and therapeutic advances.Signal transduction and targeted therapy · 2025
    Review
  9. Review
  10. Wnt/β-Catenin Signaling in Liver Pathobiology.Annual review of pathology · 2025
    Review
  11. Review
  12. Review
  13. Article
  14. Wnt/β-catenin signaling pathway in liver biology and tumorigenesis.In vitro cellular & developmental biology. Animal · 2024
    Review
  15. Review
  16. Article
  17. Haematologica · 2023
    Article
  18. Glutamine metabolic reprogramming in hepatocellular carcinoma.Frontiers in molecular biosciences · 2023
    Review
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 2 countries.

M ChiuDepartment of Biomedical Biotechnological and Translational Sciences (SBiBiT), University of Parma, Parma, Italy.
S TarditoDepartment of Biomedical Biotechnological and Translational Sciences (SBiBiT), University of Parma, Parma, Italy.
S PillozziDepartment of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy.
A ArcangeliDepartment of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy.
A ArmentoDepartment of Biomedical Biotechnological and Translational Sciences (SBiBiT), University of Parma, Parma, Italy.
J UggeriDepartment of Biomedical Biotechnological and Translational Sciences (SBiBiT), University of Parma, Parma, Italy.
G MissaleUnit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
M G BianchiDepartment of Biomedical Biotechnological and Translational Sciences (SBiBiT), University of Parma, Parma, Italy.
A BarilliDepartment of Biomedical Biotechnological and Translational Sciences (SBiBiT), University of Parma, Parma, Italy.
V Dall'AstaDepartment of Biomedical Biotechnological and Translational Sciences (SBiBiT), University of Parma, Parma, Italy.
N CampaniniDepartment of Biomedical Biotechnological and Translational Sciences (SBiBiT), University of Parma, Parma, Italy.
E M Silini1] Department of Biomedical Biotechnological and Translational Sciences (SBiBiT), University of Parma, Parma, Italy [2] Center for Translational and Molecular Oncology (COMT), University of Parma, Parma, Italy.
J FuchsDepartment of Pediatric Surgery and Urology, University Childreńs Hospital, Eberhard Karls University Tübingen, Tübingen, Germany.
S Armeanu-EbingerDepartment of Pediatric Surgery and Urology, University Childreńs Hospital, Eberhard Karls University Tübingen, Tübingen, Germany.
O BussolatiDepartment of Biomedical Biotechnological and Translational Sciences (SBiBiT), University of Parma, Parma, Italy.
University of Parma · ITUniversity of Florence · ITUniversity of Tübingen · DEOspedale di Parma · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundA subset of human hepatocellular carcinomas (HCC) exhibit mutations of β-catenin gene CTNNB1 and overexpress Glutamine synthetase (GS). The CTNNB1-mutated HCC cell line HepG2 is sensitive to glutamine starvation induced in vitro with the antileukemic drug Crisantaspase and the GS inhibitor methionine-L-sulfoximine (MSO).

methodsImmunodeficient mice with subcutaneous xenografts of the CTNNB1-mutated HCC cell lines HepG2 and HC-AFW1 were treated with Crisantaspase and/or MSO, and tumour growth was monitored. At the end of treatment, tumour weight and histology were assessed. Serum and tissue amino acids were determined by HPLC. Gene and protein expression were estimated with RT-PCR and western blot and GS activity with a colorimetric method. mTOR activity was evaluated from the phosphorylation of p70S6K1.

resultsCrisantaspase and MSO depleted serum glutamine, lowered glutamine in liver and tumour tissue, and inhibited liver GS activity. HepG2 tumour growth was significantly reduced by either Crisantaspase or MSO, and completely suppressed by the combined treatment. The combined treatment was also effective against xenografts of the HC-AFW1 cell line, which is Crisantaspase resistant in vitro.

conclusionsThe combination of Crisantaspase and MSO reduces glutamine supply to CTNNB1-mutated HCC xenografts and hinders their growth.

Indexed as

GlutamineAnimalsAntineoplastic AgentsAsparaginaseAsparaginebeta CateninCadherinsCarcinoma, HepatocellularEnzyme InhibitorsGlutamate-Ammonia LigaseHep G2 CellsHumansKi-67 AntigenLiver NeoplasmsMaleMethionine SulfoximineAntineoplastic AgentsAsparaginaseAsparaginebeta CateninCadherinsCTNNB1 protein, humanEnzyme InhibitorsGlutamate-Ammonia LigaseGlutamineKi-67 AntigenMethionine Sulfoximine

Identifiers

PMID25072259
PMCPMC4453854
OpenAlexW2067036467

What OpenQuestion holds

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LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.